Methylglyoxal-derived stress: An emerging biological factor involved in the onset and progression of cancer

Semin Cancer Biol. 2018 Apr:49:64-74. doi: 10.1016/j.semcancer.2017.05.010. Epub 2017 Jun 7.

Abstract

Cancer is a disease characterised by uncontrolled growth and proliferation of cells. Tumours primarily show a higher rate of glucose uptake for lactate production even in the presence of functional mitochondria. An important metabolic consequence is intracellular formation of glucose-derived carbonyl reactive species such as methylglyoxal (MG). It has become clear that MG is the most potent glycation agent in our body, leading to alterations of proteins and DNA, and cellular dysfunction. In recent years, emerging evidence indicates that MG plays a role in the development of cancer. This review will examine studies regarding the effects of MG on cancer onset and progression and discuss their controversies. Finally, the utilisation of inhibitors and MG scavengers will be addressed in the context of MG-mediated stress blockade for cancer therapy.

Keywords: Cancer; Glycolysis; Glyoxalase 1; Methylglyoxal stress; Warburg.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / pharmacology
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism*
  • Drug Resistance, Neoplasm
  • Gene Silencing
  • Glycolysis / drug effects
  • Glycosylation / drug effects
  • Humans
  • Lactoylglutathione Lyase / genetics
  • Lactoylglutathione Lyase / metabolism*
  • Pyruvaldehyde / antagonists & inhibitors
  • Pyruvaldehyde / metabolism*
  • Pyruvaldehyde / pharmacology
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Pyruvaldehyde
  • Lactoylglutathione Lyase